The long-term objective of this project is to use operant behavioral techniques to understand the neuroanatomical and neurochemical features of the neural network involved in processes the affective/motivation component of pain. In order to do this, we have recently developed and validated a behavioral test paradigm based on operant techniques to explore the complex nature of pain in rat models of nociception. Unlike traditional threshold measurement techniques, the general paradigm provides animals with the opportunity to perform purposeful behavior to escape and/or avoid noxious stimulation. The assumption is that escape and avoidance behavior is an indication that animals find the nociceptive stimulus to be aversive. We will test the central hypothesis of this project that the function of the anterior cingulate cortex is critical for the processing of affective and/or motivational aspects of pain processing pursuing the following two specific aims: (1) Determine the extent that the anterior cingulate cortex processes the sensory and affective/motivational component of pain. (2) Determine the relationship of the output of processing the affective/motivational component of pain to the brainstem nociceptive circuit. We hypothesize that non-pharmacological and pharmacological manipulations of the anterior cingulate cortex will selectively alter the processing of the affective/motivational component of pain and that the encoding of the affective/motivational component of pain by the anterior cingulate cortex provides input to brainstem nociceptive circuits that consequently modulates nociceptive input. Collectively, the outcomes of this project will further establish the role of the anterior cingulate cortex in processing nociceptive input. Once established, the overall goal of exploring the limbic system neural circuit related to the selection of competing motivational drives can then be explored. [unreadable] [unreadable]